The Role of Glycosylation in Inflammatory Bowel Disease

Investigating how foreign sugar modifications on anti-TNF biologics trigger immune responses in pediatric IBD patients, this project aims to personalize biologic therapy selection and inform safer drug design.
Ongoing Crohn's Disease Cross-Cutting & Special Populations Gastrointestinal Diseases Pediatric Autoimmune Diseases Ulcerative Colitis Adaptive Immunity Animal Models Autoantibodies Biological & Mechanistic Experimental Platforms & Models Human Cohorts Precision Medicine Therapeutic Development Translational & Clinical

Funding Year: 2023

Project Overview

Most biological drugs, including the anti-TNF antibodies widely used to treat inflammatory bowel disease, carry sugar modifications that differ depending on their production source. A significant proportion of IBD patients lose response to these therapies over time, and this project investigates whether foreign glycan coatings are triggering anti-drug immune responses that reduce their effective concentration. Using serum samples from a large cohort of pediatric IBD patients and a human-like mouse model, the team is characterizing anti-glycan antibody responses and comparing the efficacy of human- versus mouse-sugar-coated biologics — with the goal of informing personalized treatment strategies and improving long-term therapeutic outcomes.

Impact & Innovation

Sugar coatings as a hidden driver of drug failure.

By profiling anti-glycan immune responses in pediatric IBD patients, this project reveals how foreign sugar modifications on biologic drugs may trigger antibody responses that erode treatment efficacy over time.

  • Identifies glycan-specific immune responses as a novel, actionable mechanism underlying biologic drug failure in IBD
  • Generates IP potential through a provisional patent (Ramot 2025-022-01) and diagnostic and therapeutic tools applicable across glycosylated biologics
  • Advances the Consortium’s From Mechanistic Insight to Translation pillar by converting a molecular discovery into practical clinical guidelines for personalized IBD therapy
Research Approach

A framework designed for discovery

This project combines immunological profiling of patient samples with preclinical mouse modeling to investigate how glycosylation of anti-TNF biologics influences immune responses and drug efficacy in pediatric IBD patients. The work moves from patient cohort characterization through mechanistic analysis and in vivo validation.

Serum analysis of anti-glycan antibody responses in a large cohort of pediatric IBD patients treated with glycosylated biologics, comparative efficacy testing of human-sugar-coated versus mouse-sugar-coated drugs in a human-like mouse model, and statistical modeling to identify associations between glycan-specific immune responses and loss of drug response over time.

Serum samples from pediatric IBD patients treated with anti-TNF biologics including Infliximab, Adalimumab, and Golimumab; control healthy pediatric samples; anti-glycan antibody profiling datasets; and human-like mouse models for in vivo efficacy comparison of differentially glycosylated biologics.


Characterization of the relationship between foreign glycan recognition, anti-drug immune responses, and biologic efficacy in IBD, with the goal of generating clinical guidelines for personalized biologic therapy selection and dosing. Findings are designed to extend to broader applications in glycosylated biologic development across chronic inflammation-mediated diseases.

Investigators & Institutions

Powering the science

Principal Investigator

Vered Padler-Karavani, PhD, Colton Consortium Member

Professor, Cell Research and Immunology, Tel Aviv University

Colton Centers & Institutions

Colton Center for Autoimmunity at Tel Aviv University

Research Outputs

From insight to impact

Provisional patent submitted by Ramot (2025-022-01)